The physiological processes of both the organ of Corti and the cochlear nucleus are still incompletely understood but it is critical to learn the mechanisms which define their normal function. The physiology project advances studies which 1) are designed to learn how hair cells of the organ of Corti process complex acoustic stimuli in vivo and in vitro and 2) investigate how groups of neurons in the cochlear nucleus process complex acoustic information. In the cochlea, the approach focuses specifically on the physiology of the outer hair cells and their efferent innervation. We will measure how the olivocochlear efferent system influences hair cell potentials and if this causes mechanical responses in the cell. The experimental approach implements techniques which significantly advance the ability to measure relevant parameters. They include: simultaneous observation of receptor potentials and basilar membrane motion and positron; the use of fluorescence from molecular probes (which register physiological parameters by optical means) and the delivery of pharmacologic agents to manipulate hair cell performance and explore the efferent receptor neuropharmacology. These data will expand the knowledge of efferent physiology in the cochlea and clarify the role of outer hair cells in determining the vibrational properties of the organ. A comprehensive methodology for studying isolated hair cells in vitro will also be implemented as an essential component to the in-vivo investigations. This is centered around a workstation for the measurement of hair cell membrane potential with potentiometric dyes, motion with photodiodes, membrane currents with whole cell electrode recordings, along with the ability to apply mechanical driving forces by the entirely new approach of light-trapping. These techniques and tools are essential to increase our current level of knowledge of hair cell physiology both in vivo and in vitro.